Cells & Cellphones - Looking deep at the molecular level
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Transcript of Cells & Cellphones - Looking deep at the molecular level
“Cell’s” response to a “Cell phone/
EMF” – Looking deep at molecular
level
Dr AVS SureshMD, DM, ECMO
Consultant Hemato-Oncologist
Chief Scientific Officer & Director, ClinSync
Natural radiation
Biological life has always taken place in a sea of naturally occurring EM radiation of ◦ cosmic, ◦ atmospheric and ◦ geomagnetic origin
Electromagnetic radiation of nearly all wavelengths.
Big
bang
(13.2
bn)
Earth
forms
(4.5 bn)
Prese
nt
day
1010 109 108 107 106 105 104 103 102 101 11011
Time (years)
Big
bang
(13.2
bn)
Earth
forms
(4.5 bn)
Prese
nt
day
1010 109 108 107 106 105 104 103 102 101 11011
Magnetotact
ic
bacteria
(2 bn)
Time (years)
Big
bang
(13.2
bn)
Earth
forms
(4.5 bn)
Prese
nt
day
1010 109 108 107 106 105 104 103 102 101 11011
Magnetotact
ic
bacteria
(2 bn)
Time (years)
Bird compass
(90 m)
Big
bang
(13.2
bn)
Earth
forms
(4.5 bn)
Prese
nt
day
1010 109 108 107 106 105 104 103 102 101 11011
Magnetotact
ic
bacteria
(2 bn)
Time (years)
Bird compass
(90 m) Early man
(6 m)
Big
bang
(13.2
bn)
Earth
forms
(4.5 bn)
Prese
nt
day
1010 109 108 107 106 105 104 103 102 101 11011
Magnetotact
ic
bacteria
(2 bn)
Time (years)
Bird compass
(90 m) Early man
(6 m)
Electrification
(1878)
Man Made
The effects of artificial (man-made) EM
radiation on living tissue can be broadly
divided into two categories:
◦ Thermal effects, i.e. the destructive effects of
gross thermal heating.
◦ Athermal effects or relatively ‘weak fields’ that
produce temperature increases below the
range of normal organism fluctuations.
Slid
e 9
IS an
equation
Never will be
an equation
Living and Nonliving Objects Differ Fundamentally
Man-made EM radiation
Simple man-made (artificial) externally applied weak EM radiation currently used to test for the effects of EM radiation would also seriously need to consider that:
◦ Any complex biological modulation systems are not readily duplicated by human produced weak EM radiation as currently used for testing purposes.
◦ Effects produced by man made EM radiation may be more due to increasing the general stress load on the organism rather than because of distortion of information.
Slid
e 11
Molecular and cellular level bioeffects
of Electromagnetic Fields The studies of interactions of EMF with
biological media have been always artificial.
Possible interactions with cell membranesproposed that cell membranes could act asnon-linear resonators strongly amplifiedsignals within a narrow range of frequencies.
Effect range from nerve excitations, electronically induced forces, the dielectric breakdown of cell membranes and other processes that directly involve electric fields.
Slid
e 14
Law of Superposition
System’s
Differential
Equations
Law Holds
LawDoesn’t Hold
Linear
Nonlinear
RRM: interacting proteins have the
same frequency but opposite phase
Slid
e 16
cell
Cell
membrane
p1 f1 p2 f2 p3 f3
DNA
Sinusoids of the same frequency but different phase
Why should we be worried so
much about the DNA The functionality of a given cell goes with
specific orders given by DNA
Periodic simple- AAAA
Periodic complex- CAT CAT
Complex- non informative--- AKJLHA
DHA SKDSK
Complex- informative- NOTE THIS
POINT
Why should we be worried so
much about the DNA The functionality of a given cell goes with
specific orders given by DNA
Periodic simple- AAAA
Periodic complex- CAT CAT
Complex- non informative--- AKJLHA
DHA SKDSK
Complex- informative- NOT THIS POINT
Postulate: proteins interact through oscillations of a
physical field possibly electromagnetic
charge transfer through the protein backbone is a sufficient condition for EM radiation/absorption
W= W(COOH)-W(NH2) = 0.13 Ry.
Vmax =
where e is the electron charge, and m is electron mass.
V < 7.87 x 10 5 m/sec
distance between amino acids could be considered at:
d= 3.8 Å
Fmax < V/(2d); Fmin =2 Fmax/N,
where N = total number of amino acids
Fmax < 1x1015 Hz, Lmin > 330 nm
Fmin > 1x 1013 Hz, Lmax < 30000 nm
meW2
Slide 19
Human DNA is ~2meters long and has ~3 billion base pairs
-230 -160 +1 (bp)-320 -192 -107 -68-100-166
HSPMYC A
HSP70
Sp1 AP-2 HSE Sp1 AP-2 HSE SRE
ATF
TATA
Sp1 AP-2
HSPMYC C
HSPMYC B
Heat Shock Domain
(thermal)
EMF Domain
(non-thermal)
.
EMF Specific Domain in HSP70
Lin et al (1999) J Cellular Biochem 75:170-176.
EMF-Specific DNA can be moved
counts
Chloramphenicol transferase
(CAT) Activity
0
10
20
30
40
50
60
Background
EM
Negative Control
Luciferase Activity
counts
0
10
20
30
40
50
60
Background
EM
Negative Control
Experimental Conditions Experimental Conditions
Lin et al (2001) J Cellular Biochem 81:143-148.
The next 2 important questions
So What?
Who cares?
There are 260 million known mutation
associated with cancer
But only 26 are proven to cause the
cancer beyond doubt
Primary
detection
Subsequent
responseMF
Common question:
Given that we are all exposed to the geomagnetic field of 50 mT, how can a 50 Hz 0.4 mT field make any difference?
The primary physics detector, only has
to detect
It is the subsequent biological response that
matters
Primary
detection
Subsequent
responseMF
Common question:
Given that we are all exposed to the geomagnetic field of 50 mT, how can a 50 Hz 0.4 mT field make any difference?
The primary physics detector, only has
to detect
It is the subsequent biological response that
matters
The Point?
A scientist must keep an open mind
and be able and willing to let go of
their paradigms and their models –
otherwise we develop of a culture of
scientists interfering with science
Rhythmic signals and behaviour of
the human body
Life processes in any biological organism are
usually based on rhythmic oscillations:
Electrophysiological signals such as ECG, EEG, EMG
Hormonal/biochemical rhythms such as circadian
rhythms
Electrical and electromagnetic resonances in the body,
particularly at the cell level
Slid
e 27
To try to understand the epidemiological findings, lets consider
three physical interaction mechanisms and some biology
So-called Ion Cyclotron Resonance (ICR) models
and Ca2+ efflux from cells
Circadian rhythm and melatonin disruption
could potentially explain many of the health effects
Biogenic Magnetite
in animals & humans
Radical Pair Mechanism (RPM) at low fields
Mechanisms
Cryptochromes in birds and in man
Background:
Increased Ca2+ efflux from brain tissues with ELF modulated RF EMFs (Bawin et al. 1975, Blackman et al. 1979, 1980a, b, Adey et al. 1982), and with ELF electric fieldswithout an RF carrier (Bawin & Adey 1976).
Observations:
Increased Ca2+ efflux from brain tissue at particular frequencies of an applied magnetic field in the same vector direction as Earth’s natural DC field (Blackman et al 1985).
Overall findings:
Liboff (2006)1 cites 71 papers, on this apparent ‘window’ or ‘resonance’ phenomenon’ with only 11 reporting negative findings.
Today >150 papers in model systems: bone, cell culture, rat behaviour, neural cell culture, diatom motility, complex biological systems, plants, cell-free systems.
Explanation:
In a magnetic field, Ca2+ and other ions behave like a physics cyclotron and so response can be ‘tuned’ to the cyclotron frequency – hence ‘ICR’.
Status:
However, ICR may be an inappropriate analogy – unlike a real cyclotron, Ca2+
ions are not in a vacuum.
Ca2+ efflux and Ion Cyclotron Resonance (ICR) models
1Liboff 2006 Chapter 9. In Bioengineering and biophysical aspects of EMFs p261-292. Eds Barnes & Greenebaum. 1 edition (7 Nov 2006) CRC Press
DCBm
qf
2
1
r
mField BDC x
rmvBqvF 2
fr
v 2
For Ca2+, q=2, m = mass of Ca ion
e.g. at BDC = 50 mT, f = 40 Hz
Bawin et al. 1975 PNAS 247:74-81; Bawin & Adey 1976 PNAS 73:1999-2003 [10 – 15 V/m in air; 0.1 mV/cm in tissue]Gavalas-Medici & Day-Magdaleno 1976 Nature 261:256-259. Blackman et al. 1985 Bioelectromagnetics 6:327-37.
Physical interaction mechanisms and some biology
So-called Ion Cyclotron Resonance (ICR)
and Ca2+ efflux from cells
Circadian rhythm and melatonin disruption
could potentially explain many of the health effects
Biogenic Magnetite
in animals & humans
Radical Pair Mechanism (RPM) at low fields
Mechanisms
Cryptochromes in birds and in man
Physical interaction mechanisms and some biology
So-called Ion Cyclotron Resonance (ICR)
and Ca2+ efflux from cells
Circadian rhythm and melatonin disruption
could potentially explain many of the health effects
Biogenic Magnetite
in animals & humans
Radical Pair Mechanism (RPM) at low fields
Mechanisms
Cryptochromes in birds and in man
Magnetite and other iron-mineral particles in animals and man
All possess biogenic magnetite or other membrane bound iron-mineral particles (magnetosomes) used for
navigation
(magnetic sensitivity exists in all major groups of vertebrate animals, as
well as in some molluscs, crustaceans and insects, including flies, chickens
and mole rats)
U = - μ.B where μ = v M
U = potential energy of dipole magnet in field B
m = magnetic moment
v = particle volume; r = radius
M = 4.8 x 105 J T-1 m-3
k = Boltzmann’s constant, 1.3807 x 10-23 J K-1,
and T the absolute temperature.
The energy required to rotate the particle 180° is 2U,
compare this to the thermal energy kT at 300° K
Potential energy of magnetic particle in the Earth’s field
- Compare this with the thermal energy kT
But the sensitivity is magnified with arrays & clusters of iron-based
minerals
Mag
net
ic F
ield
B
0
500
1000
1500
0 100 200 300 400 500 600
Diameter, 2r nm
Ra
tio
of
MF
en
erg
y t
o k
T
50
µT
0
10
20
30
40
50
60
0.4
µT
50 µT
0.4 µT
0
1
0 50 100 150 200 250 300
Particles of interest:
Single domain Superparamagnetic (sp)
Whole particle rotates Particle remains stationary but MF vector
flips
Pigeons
Solov’yov & Greiner 2007 Biophys J 93:1493–1509
- force of 0.2 pN sufficient to excite channels in nerve cell
Fleissner et al. Naturwissenschaften 94:631–642 (2007)
using μ-SXRF and μ-XANES.
Magnetite structures could
transduce 50 Hz MFs at 0.5 mT:
Vanderstraeten & Gillis (2010)
Bioelectromagnetics 31:371-
379
Similar structures in chickens,
European Robin and Garden
Warbler
Maghemite: 3
3
2 OFe
4
3
2
2 OFeFe
Magnetite:
In pigeons, the inclination sensitivity is 0.02 - 0.17 degrees, down to 0.01 mT (~10 nT) - Gould 2010 Current Biol 21;R226
<30 nm30 – 200 nm
5 mm─
Trigemina
l
nerve
10 mm
Physical interaction mechanisms and some biology
So-called Ion Cyclotron Resonance (ICR)
and Ca2+ efflux from cells
Circadian rhythm and melatonin disruption
could potentially explain many of the health effects
Biogenic Magnetite
in animals & humans
Radical Pair Mechanism (RPM) at low fields
Mechanisms
Cryptochromes in birds and in man
Introduction to RPM – Zeeman splitting and Larmor
precession
hυ
En
erg
y+ 1/2
- 1/2
B-F
ield
(a) (b)
No field Applied field
Spin
direction
Precession of electron spin
vector with frequency
B-F
ield
At the GM field in Nottingham, 50 mT:- h is ~10-7 of thermal energy kT
The equivalent classical
model has the electron spin
vector precessing at the
Larmor frequency of 1.4
MHz at 50 mT
Pieter Zeeman
(1865-1943)
Zeeman Effect
1896
Joseph Larmor
(1857-1942)
Get resonant absorption (ESR) at frequency
= 1.4 MHz at 50 mT
In a static MF, get splitting of
spectral lines due to the electron
spin
RPM and the Low Field Effect
Singlet
productsTriplet
products
Electron
transfer
Magnetic nuclei
+ external field
Blue-light photon
(Different products)
S↔T mixing
S T
Woodward et al. 2009 Biochem Soc Trans 37(2):358-62
At low fields* get an increased rate of S-T conversionT-state radical pairs cannot recombine, so they react elsewhere, e.g. with DNA
*for GM field sensitivity, requires RP lifetimes ~1 us
If both radicals experience the same MF, no S-T mixing occurs
If each radical experiences a different MF, S-T mixing may occur
1 2
Unpaired electron
- radical 1
(precesses about B1)
Unpaired electron
- radical 2
(precesses about B2)
Both radicals see the Earth’s magnetic field, 50 mT, in
addition to any internal fields
At the low fields of interest, the radical pair needs to live for ~1 ms, for S-T mixing to evolve
B1 B2
EMF for Health Conditions
Fracture non-union – 65-75Hz
Congenital pseudoarthrosis – 15Hz
Osteoporosis – 72Hz
Hip arthroplasty – 50Hz
Arthritis – 50Hz
Tinnitus – 0.5-17Hz
Rotator Cuff Tendonitis – 71-75Hz
Venous skin ulcers – 75Hz
Multiple sclerosis – 4-13Hz
(Shupak, 2003)
PEMF Cellular Effects
Increases osteoblast intracellular calcium & alters
response to epidermal growth factor.(Shigaku,1990)
Stimulates production of type-I collagen,
osteocalcin, & osteopontin.(Cornaglia, et al., 2006)
Antiinflammatory effect via restoration of plasma
membrane calcium ATPase activity.
(Selvam, et al., 2007)
Conclusions
EMF had some effect on cells
What it will lead is not known
We can say that in last 140 years of electromagnetic emission from high tension lines, no observable adversities notes
No proven AE from cells at cellular level
The results are not enough to support the apprehensions
Care is always advisable
Conclusion